Conduct Disorder
Conditions
Keywords
Aripiprazole
Brief summary
The proposed study will be a 6-week open label study evaluating aripiprazole in the treatment of 12 male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder. The initial dose depending on the weight of the patient will be as follows: \< 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 kg = 5 mg/d; \> 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). For the first two weeks of the study, the dose will be flexible based on response and tolerance and thereafter will remain fixed.
Detailed description
The use of atypical antipsychotics in children began in 1992 with several small case series with clozapine. Since that time, five other atypical agents, risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole have been introduced into the US market. The newer atypical agents are not associated with agranulocytosis that has limited the usefulness of clozapine. Among the atypical antipsychotics, risperidone has remained the most extensively studied in children and adolescents, for a variety of problems, including Tourette's disorder, conduct disorder, schizophrenia, aggression, and pervasive development disorder. Risperidone has been shown to be an effective treatment in many of these disorders. However, weight gain, hyperprolactinemia, and extrapyramidal symptoms (EPS) are troublesome adverse effects more commonly associated with risperidone such that the drug's utility in this aged patient population is limited. We expect that the utility of aripiprazole in treating the pediatric population will not be limited by adverse effects like the other atypical antipsychotics.
Interventions
DRUGAripiprazole
The initial dose depending on the weight of the patient will be as follows: \< 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 kg = 5 mg/d; \> 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). Thereafter the dose will be flexible based on response and tolerance for the duration of the 6 week study. All subjects initially received either a 5 or 10 mg/d (7.0 ± 2.6 mg/d) dose of aripiprazole. Thereafter the dose was individualized based on response and tolerance. Maximum dose was 20 mg.
Sponsors
Bristol-Myers Squibb
University of Iowa
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
open label trial
Eligibility
Sex/Gender
MALE
Age
13 Years to 17 Years
Healthy volunteers
Yes
Inclusion criteria
* Male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder.
Exclusion criteria
* Clinically significant laboratory and/or ECG abnormalities * Pre-existing health conditions that would compromise patient safety * Mental retardation * Previous use of aripiprazole * Active psychosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Outcome Efficacy Measure: Rating of Aggression Against People and/or Property Scale (RAAPP) (Kemph et al 1993) | 6 weeks | Rating of Aggression Against People and/or Property Scale (RAAPP) (Kemph et al 1993) is a global rating scale of aggression completed by clinicians. Score given based on following severity scale with subject assigned 1 number: Intolerable behavior-frequently physically attacks others and destroys property (5); Severe-occasionally physically attacks people and destroys property (4); Moderately 21); and No aggressiveness reported (1). A minimum score of 1 is best and a maximum score of 5 is worst. There are no subscale scores. |
| Overt Aggression Scale-Modified (OAS-M) | 6 weeks | OAS-M divides aggressions into 4 subtypes: 1) verbal aggression, 2) property aggression, 3) self aggression (autoaggression), and 4) physical aggression. Each subtype has an initial score ranging from 0 (least aggressive) to 4 (most aggressive). The score for each subscale is further weighed (multiplied) by a constant: verbal scale's constant is 1 (max adjusted score of 4); property scale's constant is 2 (max adjusted score 8); self scale's constant is 3 (max adjusted score 12); and physical scale's constant is 4 (max adjusted score of 16). Within a given scale, 0 is the best score and maximum adjusted scale score is worst. |
| Children's Aggression Scale-Parent Version | 6 weeks | CAS-P is a 33 item scale representing 5 domains of aggression: Items in a domain were computed based on two reference points. The first was based on a 5 point frequency range with 0 being best (never) and 4 (\> 10 times being) worst. These same items were then adjusted such that more severe acts would be weighted more heavily compared to less severe aggressive behaviors. Within a domain, 0 was the best score. Worst score for the various aggression domains were: Verbal 26.16, Against Objects and Animals 11.8, Provoked 15.84, Initiated 17.84, and Use of Weapons 13.16. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Outcome Measures Were the Clinical Global Impression-Severity (CGI-S) Scale (NIMH, 1985a). | 6 weeks | The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Possible ratings are: 1. Normal, not at all ill; 2. Borderline mentally ill, 3. Mildly ill; 4. Moderately ill; 5. Markedly ill; 6. Severely ill; or 7. Among the most extremely ill patients. |
| Secondary Outcome Measures Were the Clinical Global Impression--Improvement (CGI-I) Scales (NIMH, 1985a). | 6 weeks | The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1. Very much improved; 2. Much improved; 3. Minimally improved; 4. No change; 5. Minimally worse; 6. Much worse; or 7. Much worse) |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited through the child psychiatric clinic after being identified as diagnosed with DSM 4 conduct disorder. Subjects and their parents were approached about participation in the study. Recruitment time was November 2004 through March 2009
Pre-assignment details
The study was an open label study with no separate treatment groups, i.e., different doses or placebo. All subjects that were enrolled into participation were entered into active treatment.
Participants by arm
| Arm | Count |
|---|---|
| Aripiprazole Treatment of Conduct Disorder The study was a 6-week open label study evaluating aripiprazole in the treatment of 12 male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder (American Psychiatric Association 2000). | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 2 |
Baseline characteristics
| Characteristic | Aripiprazole Treatment of Conduct Disorder |
|---|---|
| Age, Categorical <=18 years | 10 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 14.6 years STANDARD_DEVIATION 1.1 |
| Children's Aggression Scale-Parent Version Agression Against Objects and Animals | 3.8 units on a scale STANDARD_DEVIATION 2.2 |
| Children's Aggression Scale-Parent Version Initiated Aggression | 1.6 units on a scale STANDARD_DEVIATION 2 |
| Children's Aggression Scale-Parent Version Provoked Aggression | 2.1 units on a scale STANDARD_DEVIATION 2.2 |
| Children's Aggression Scale-Parent Version Use of Weapons | 0.4 units on a scale STANDARD_DEVIATION 1 |
| Children's Aggression Scale-Parent Version Verbal Aggression | 12.9 units on a scale STANDARD_DEVIATION 4.3 |
| Overt Aggression Scale-Modified (OAS-M) (Kay et al 1988) OAS-M, aggression against property | 4.2 weighted scores on a scale STANDARD_DEVIATION 3 |
| Overt Aggression Scale-Modified (OAS-M) (Kay et al 1988) OAS-M, autoaggression | 0.6 weighted scores on a scale STANDARD_DEVIATION 1.9 |
| Overt Aggression Scale-Modified (OAS-M) (Kay et al 1988) OAS-M, physical aggression | 4.5 weighted scores on a scale STANDARD_DEVIATION 3.9 |
| Overt Aggression Scale-Modified (OAS-M) (Kay et al 1988) OAS-M, verbal aggression | 2.2 weighted scores on a scale STANDARD_DEVIATION 1.2 |
| Rating of Aggression Against People and/or Property Scale | 3.0 scores on a scale STANDARD_DEVIATION 0.9 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Children's Aggression Scale-Parent Version
CAS-P is a 33 item scale representing 5 domains of aggression: Items in a domain were computed based on two reference points. The first was based on a 5 point frequency range with 0 being best (never) and 4 (\> 10 times being) worst. These same items were then adjusted such that more severe acts would be weighted more heavily compared to less severe aggressive behaviors. Within a domain, 0 was the best score. Worst score for the various aggression domains were: Verbal 26.16, Against Objects and Animals 11.8, Provoked 15.84, Initiated 17.84, and Use of Weapons 13.16.
Time frame: 6 weeks
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aripiprazole Treatment of Conduct Disorder | Children's Aggression Scale-Parent Version | Verbal Aggression | 2.7 units on a scale | Standard Deviation 2.8 |
| Aripiprazole Treatment of Conduct Disorder | Children's Aggression Scale-Parent Version | Aggression Against Objects and Animals | 0.4 units on a scale | Standard Deviation 0.8 |
| Aripiprazole Treatment of Conduct Disorder | Children's Aggression Scale-Parent Version | Provoked Aggression | 1.6 units on a scale | Standard Deviation 0.5 |
| Aripiprazole Treatment of Conduct Disorder | Children's Aggression Scale-Parent Version | Initiated Aggression | 0.6 units on a scale | Standard Deviation 1.2 |
| Aripiprazole Treatment of Conduct Disorder | Children's Aggression Scale-Parent Version | Aggression with Use of Weapons | 0.1 units on a scale | Standard Deviation 0.3 |
Primary
Overt Aggression Scale-Modified (OAS-M)
OAS-M divides aggressions into 4 subtypes: 1) verbal aggression, 2) property aggression, 3) self aggression (autoaggression), and 4) physical aggression. Each subtype has an initial score ranging from 0 (least aggressive) to 4 (most aggressive). The score for each subscale is further weighed (multiplied) by a constant: verbal scale's constant is 1 (max adjusted score of 4); property scale's constant is 2 (max adjusted score 8); self scale's constant is 3 (max adjusted score 12); and physical scale's constant is 4 (max adjusted score of 16). Within a given scale, 0 is the best score and maximum adjusted scale score is worst.
Time frame: 6 weeks
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aripiprazole Treatment of Conduct Disorder | Overt Aggression Scale-Modified (OAS-M) | verbal aggression | 1.0 units on a scale | Standard Deviation 1.2 |
| Aripiprazole Treatment of Conduct Disorder | Overt Aggression Scale-Modified (OAS-M) | property aggression | 0.6 units on a scale | Standard Deviation 1.9 |
| Aripiprazole Treatment of Conduct Disorder | Overt Aggression Scale-Modified (OAS-M) | self aggression | 0.6 units on a scale | Standard Deviation 1.9 |
| Aripiprazole Treatment of Conduct Disorder | Overt Aggression Scale-Modified (OAS-M) | physical aggression | 1.6 units on a scale | Standard Deviation 3.9 |
Primary
The Primary Outcome Efficacy Measure: Rating of Aggression Against People and/or Property Scale (RAAPP) (Kemph et al 1993)
Rating of Aggression Against People and/or Property Scale (RAAPP) (Kemph et al 1993) is a global rating scale of aggression completed by clinicians. Score given based on following severity scale with subject assigned 1 number: Intolerable behavior-frequently physically attacks others and destroys property (5); Severe-occasionally physically attacks people and destroys property (4); Moderately 21); and No aggressiveness reported (1). A minimum score of 1 is best and a maximum score of 5 is worst. There are no subscale scores.
Time frame: 6 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole Treatment of Conduct Disorder | The Primary Outcome Efficacy Measure: Rating of Aggression Against People and/or Property Scale (RAAPP) (Kemph et al 1993) | 1.7 units on a scale | Standard Deviation 0.8 |
Secondary
Secondary Outcome Measures Were the Clinical Global Impression--Improvement (CGI-I) Scales (NIMH, 1985a).
The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1. Very much improved; 2. Much improved; 3. Minimally improved; 4. No change; 5. Minimally worse; 6. Much worse; or 7. Much worse)
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole Treatment of Conduct Disorder | Secondary Outcome Measures Were the Clinical Global Impression--Improvement (CGI-I) Scales (NIMH, 1985a). | 2.1 units on a scale | Standard Deviation 1.4 |
Secondary
Secondary Outcome Measures Were the Clinical Global Impression-Severity (CGI-S) Scale (NIMH, 1985a).
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Possible ratings are: 1. Normal, not at all ill; 2. Borderline mentally ill, 3. Mildly ill; 4. Moderately ill; 5. Markedly ill; 6. Severely ill; or 7. Among the most extremely ill patients.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole Treatment of Conduct Disorder | Secondary Outcome Measures Were the Clinical Global Impression-Severity (CGI-S) Scale (NIMH, 1985a). | 3.0 units on a scale | Standard Deviation 1.5 |